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DOI: 10.1055/s-0031-1290081
Titanium(IV) Enolates of 2-Nitrocarboxylic Esters and Their Oxidative Chlorination. A Convenient Route to α-Chloro-α-nitrocarboxylates
Publication History
Publication Date:
03 January 2012 (online)
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Abstract
A new method for the synthesis of 2-chloro-2-nitrocarboxylic esters from 2-nitrocarboxylates is described. The procedure consists of the oxidative chlorination of titanium(IV) enolates of 2-nitro esters in the presence of ammonium nitrate. Esters of 2-chloro-2-nitrocarboxylic acids are formed in very good to quantitative yields. Application of this method for the chlorination of α,α′-dinitrodicarboxylates leads to α,α′-dichloro-α,α′-dinitrocarboxylic esters with high meso-diastereoselectivity. The absence of ammonium nitrate from the reaction mixture affects the reduction of nitro groups and leads to partial transformation of 2-nitrocarboxylic esters into 2-(hydroxyimino)carboxylates.
Key words
oxidative chlorination - titanium enolates - diastereoselectivity - esters - transition states
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- Supporting Information
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References and notes
Crystallographic data (excluding structure factors) for the structure of 3g have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 843131. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033 or e-mail: deposit@ccdc.cam.ac.uk
21Oxidative chlorination of α-nitrocarboxylic esters; representative synthesis of 3e: A solution of dimethyl 2,7-dinitrooctanedioate²4 (1e; 1.08 g, 3.69 mmol) in CH2Cl2 (40 mL) was cooled under argon to -15 ˚C and TiCl4 (0.90 mL, 1.55 g, 8.16 mmol, 2.2 equiv) was added in one portion. The reaction mixture was stirred for 20 min, then DIEA (1.41 mL, 1.05 g, 8.16 mmol, 2.2 equiv) in CH2Cl2 (4 mL) was added dropwise to form the orange titanium(IV) enolate. The ice bath was removed and the solution was gradually warmed to r.t. Fine pulverized ammonium nitrate NH4NO3 (0.59 g, 7.38 mmol, 2 equiv) was added and the flask was protected against moisture. The reactants were stirred for 7 days, then the solution was poured into concentrated aqueous NH4Cl (60 mL), stirred, and the lower organic layer was separated and dried with anhydrous MgSO4. The crude product isolated after evaporation of CH2Cl2 and purified by column chromatography (silica gel, 230-400 mesh; CHCl3-MeOH, 30:1) to give 3e (1.13 g) as a colorless solid. Mp = 77-78 ˚C. TLC: R f = 0.70 (Merck silica gel 60; CHCl3-MeOH, 30:1). Anal. Calcd for C10H14Cl2N2O8: C, 33.26; H, 3.91; N, 7.76. Found: C, 33.41; H, 3.99; N, 7.59. ¹H NMR (CDCl3, 300 MHz): δ = 3.90 (s, 6 H, OCH3), 2.63 (m, 2 H, CH aHb), 2.48 (m, 2 H, CHa H b), 1,67 (m, 2 H, CH cHd), 1.35 (m, 2 H, CHc H d). ¹³C NMR (CDCl3, 75 MHz): δ = 163.1 (COOMe), 101.5 (C-NO2), 54.7 (OCH3), 38.3 (CH2), 22.6 (CH2). IR (ATR): 2959, 1756, 1566, 1436, 1343, 1264, 1242, 1179, 1103, 1010 cm-¹. GC/MS (EI): m/z (%) = 268 (6) [M+ - NO2 - NO2 - H], 238 (32) [M+ - NO2 - NO2 - CH3OH], 236 (41) [M+ - Cl - COOCH3 - OCH3], 209 (9) [M+ - H - C(Cl)(NO2)COOCH3], 168 (100) [M+ - NO2 - NO2 - Cl - Cl - OCH3]
23Reduction of the radical intermediate 7 with Ti(III) ions gives only one isomer of two possible 2-(hydroxyimino) esters. Based on the analysis of the NMR spectra measured for by-product 4a, we have determined its structure as ethyl (E)-2-(hydroxyimino)propanoate. Indeed, our assignment has been confirmed by the literature data. Stereoselective formation of (E)-2-(hydroxyimino)carboxylates indicates that the nitro group loses an oxygen atom adjacent to the ester group during reduction. This observation is very helpful for investigation of the transition state. For NMR data of ethyl (E)-2-(hydroxyimino)propanoate, see: (a) Lampeka, R. D.; Silva, T. Yu.; Skopenko, V. V. Zh. Obshch. Khim. 1989, 59, 1252. (b) Pitts, M. R.; Harrison, J. R.; Moody, C. J. J. Chem. Soc., Perkin Trans. 1 2001, 955. (c) For NMR data of ethyl (Z)-2-(hydroxyimino)propanoate, see: Beraud, V.; Perfetti, P.; Pfister, C.; Kaafarani, M.; Vanelle, P.; Crozet, M. P. Tetrahedron 1998, 54, 4923.
25Oxidative chlorination of ethyl nitroacetate does not lead to the expected ethyl chloronitroacetate but gives, instead, ethyl chloro(hydroxyimino)acetate as a main product.